In the Lab, Recreating HIV’s Hidden Reservoirs

By Jeffrey Laurence, M.D.

Dr. Alberto Bosque

February 9, 2011— One major obstacle to curing HIV is the persistence in tissues of latent virus that is resistant to attack by current antiretroviral therapies (ART). Recent studies—including several published by amfAR grantees—have documented encouraging progress in the search for the reservoirs where virus persists. But even after zeroing in on HIV’s hiding places, scientists need simple, clinically relevant test-tube models for testing new means of attacking the virus in these reservoirs. Dr. Alberto Bosque, one of amfAR’s Mathilde Krim Fellows in Basic Biomedical Research, has helped to develop one such system.

Writing in the January issue of the research journal Methods, Bosque and his mentor, Dr. Vicente Planelles, of the University of Utah, review problems with older models of HIV latency. They then offer their novel means of producing large numbers of latently infected cells. These special T cells, known as CM or central memory cells, are not derived from artificial cell lines but taken directly from human blood. CM cells have been shown by amfAR fellow Dr. Nicolas Chomont and others to constitute the main reservoir for HIV in the blood, lymph glands, and intestines.

Bosque’s method involves extracting unstimulated or “naïve” CD4+ T cells from the blood of uninfected, healthy donors using antibodies and magnetic columns. He and his colleagues then broadly stimulate these cells with a cocktail of five immune hormones and antibodies. Four days later they infect these cells with a special form of HIV that has been genetically disabled so that it can’t spread outside of the first cell it infects. These cells, harboring latent HIV, can be maintained with T-cell growth factors, releasing substantial amounts of virus only when stimulated. Bosque and Planelles hope to use these cells to define how various stimuli induce latent viruses to start replicating, thereby rendering them vulnerable to existing anti-HIV drugs.

The authors conclude that no single test-tube or animal model for HIV latency is likely to capture the broad spectrum of means by which HIV hides or becomes activated. But their new system brings us one step closer to defining critical factors involved in maintaining latent HIV, with the ultimate aim of rationally designing drugs to destroy such viruses.